O-GlcNAc signaling increases neuron regeneration through one-carbon metabolism in Caenorhabditis elegans.

Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked ß-N-acetylglucosamine (O-GlcNAc) signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration. Here, we define the specific metabolic pathway by which O-GlcNAc transferase (ogt-1) loss of function mediates increased regenerative outgrowth. Performing in vivo laser axotomy and measuring subsequent regeneration of individual neurons in C. elegans, we find that glycolysis, serine synthesis pathway (SSP), one-carbon metabolism (OCM), and the downstream transsulfuration metabolic pathway (TSP) are all essential in this process. The regenerative effects of ogt-1 mutation are abrogated by genetic and/or pharmacological disruption of OCM and the SSP linking OCM to glycolysis. Testing downstream branches of this pathway, we find that enhanced regeneration is dependent only on the vitamin B12 independent shunt pathway. These results are further supported by RNA sequencing that reveals dramatic transcriptional changes by the ogt-1 mutation, in the genes involved in glycolysis, OCM, TSP, and ATP metabolism. Strikingly, the beneficial effects of the ogt-1 mutation can be recapitulated by simple metabolic supplementation of the OCM metabolite methionine in wild-type animals. Taken together, these data unearth the metabolic pathways involved in the increased regenerative capacity of a damaged neuron in ogt-1 animals and highlight the therapeutic possibilities of OCM and its related pathways in the treatment of neuronal injury.

Maternal and Obstetric Factors Associated with Low Birth Weight.

BACKGROUND: Low birth weight is a factor associated with perinatal, neonatal and post-neonatal morbidity and mortality and is associated with development of chronic diseases in adulthood. This study aimed to identify the maternal and obstetric factors associated with low birth weight in selected hospitals of Nepal. METHODS: Matched case control study was conducted in two tertiary level hospital of Nepal during May 2017 to April 2018. There were 368 mothers with single full term live low birth weight babies (cases) and 736 mothers with single full term live normal birth weight babies (controls) matched on babies' gender and place of delivery included in the study. Multivariable conditional logistic regression analysis was used to eliminate the effects of potential confounders and to identify the independent effect of various risk factors associated with low birth weight. RESULTS: A total of 1104 respondents (1 case : 2 controls) were included in the study. Multivariable conditional logistic regression analysis revealed that maternal height <146 cm [AOR 5.14, (95%CI:2.03-13.01),(p=0.001)], maternal weight ?50 kg [AOR 3.75,(95%CI:2.15-6.56), (p<0.001)], primi-parity [AOR 4.58, (95%CI:1.71-12.25),(p=0.002)], multi-parity [AOR 3.01,(95%CI: 1.11-8.12),(p=0.030)], rest in day time ?2 hours [AOR 3.68, (95%CI: 2.01-6.75),(p<0.001)], rest in night time for <8 hours [AOR 5.76, (95%CI: 2.32-14.33), (p<0.001)], Iron and folic acid consumption for ?60 days [AOR 5.47, (95%CI: 2.73-10.95),(p<0.001)], Iron and folic acid consumption for 61-120 days [AOR 3.04, (95%CI: 1.90-4.87),(p<0.001), no calcium consumption [AOR 3.00, (95%CI: 1.78-5.04),(p<0.001)] were the significant risk factors associated with Low birth weight Conclusions: Height and weight of women, parity, duration of rest in day time and night time, consumption of Iron and folic acid and calcium were the maternal and obstetric determinants for the occurrence of low birth weight.